Clinical Trial: Clinical Trial to Assess Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multiple System Atrophy of the Parkinsonian Subtype (MSA-P)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Multi-centered, Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess the Efficacy, Safety, and Tolerability of Rasagiline Mesylate 1 mg in Patients With Multip

Brief Summary: To test the clinical effect of rasagiline on subjects with MSA of the parkinsonian subtype.

Detailed Summary:
Sponsor: Teva Pharmaceutical Industries

Current Primary Outcome: Change From Baseline to Week 48/Termination Visit in the Total Unified Multiple System Atrophy Rating Scale (UMSARS Part I and II) [ Time Frame: Day 0 (baseline), Week 48 ]

This outcome represents the sum of 2 UMSARS sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement.

In the case that 6 items or more (out of 26) were missing at a certain visit, the UMSARS score for that visit was assigned a missing value.



Original Primary Outcome: Change from baseline to Week 48/Termination visit in the total UMSARS score [ Time Frame: 48 weeks ]

Current Secondary Outcome:

  • Clinical Global Impression Improvement (CGI-I) at Week 48/Termination Visit [ Time Frame: Week 48 ]

    Outcome measures the investigator's clinical impression of the participants' improvement at Week 48 as compared to Week 12. CGI scale range from 1-7, with 1=very much improved, 4= no change, and 7=very much worse.

    In order to maintain the overall (hypotheses about primary and key secondary endpoints) type I error at the 0.05 level an hierarchy will be employed as follows: If the primary endpoint will be found to be significant at a significance level of 0.05 then the first key secondary endpoint will be tested, if this endpoint will be found to be significant in a significance level of 0.05 then the second key secondary endpoint will be tested and so on. The 'key' secondary endpoints are outcomes 2-6.

  • Change From Baseline to Week 24 in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score [ Time Frame: Day 0 (baseline), Week 24 ]

    The UMSARS is composed of 2 sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement.

    In the case that 6 items or more (out of 26) were missing at a certain visit, the UMSARS score for that visit was assigned a missing value.

  • Percentage of Participants Who Achieved a Score of >=3 on the Unified Multiple System Atrophy Rating Scale (UMSARS) Question #7 Regarding Ambulation [ Time Frame: up to week 48 ]
    UMSARS' Question #7 concerns the participant's ability to walk, rated on a scale of 0=normal to 4=cannot walk at all even with assistance. This endpoint counts participants rated a 3 or worse. Rating 3 = Severely impaired; assistance and/or walking aid needed occasionally.
  • Mean Score of the Composite Autonomic Symptom Scale Select (COMPASS_Select Change) at Week 48/Termination Visit [ Time Frame: 48 weeks ]
    COMPASS_Select change is comprised of 5 of the 11 domains in the COMPASS scale: Orthostatic Intolerance, Bladder Disorder, Sweating, Vasomotor, and Sleep Disorder COMPASS_Select change has a range of -150 to 150, with -150 indicating symptoms are much better and 150 indicating symptoms are much worse.
  • Change From Baseline to Week 48/Termination Visit in the Multiple System Atrophy (MSA) Health-related Quality of Life (QoL) Scale [ Time Frame: Day 0 (baseline), Week 48 ]
    The Multiple System Atrophy Quality of Life questionnaire (MSA-QoL) is a self-reported questionnaire focusing on MSA-specific symptoms and has a scale ranging from 0 - 160, with 0= 'no problem' and 160= "extreme problem".
  • Rate of Progression in Total Unified Multiple System Atrophy Rating Scale (UMSARS) Score From Baseline to Weeks 12-48 [ Time Frame: Day 0 (baseline), Weeks 12-48 ]

    The UMSARS is composed of 2 sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment.

    The rate of progression of atrophy is represented by the slope of change from baseline scores for visits between Weeks 12 and 48.

  • Change From Baseline to Week 48 or Termination in UMSARS Subscores for Parts I, II and IV [ Time Frame: Day 0 (baseline), Week 48 or termination visit ]
    UMSARS Part I is an historical review and scores symptoms of neurological and autonomic dysfunction with 12 items rated on a scale of 0 (normal) to 4 (extreme dysfunction). The full scale for Part 1 is therefore 0 (normal) to 48 (extreme dysfunction). Part II is a motor examination and has 14 items also rated on a scale of 0 to 4 for a full scale of 0 (normal) to 56 (extreme dysfunction). Part IV is a global disability scale with rates the extent of disease from 1 (normal) to 5 (severe disease).
  • Change From Baseline to Week 12 in Total UMSARS Score for Symptomatic Effect [ Time Frame: Day 0 (baseline), Week 12 ]
    This outcome represents the sum of 2 UMSARS sub-scales: Part I: Historical Review that includes 12 items and Part II: Motor Examination that includes 14 items. All items range from 0 to 4. Each subscale score is the sum of its items and the total UMSARS score is the sum of all 26 items. Hence the total UMSARS score can range from 0 to 104, with 0 meaning no impairment and 104 indicating severe impairment. Negative change from baseline scores indicate improvement.

  • Original Secondary Outcome:

    • Change from baseline to week 24 in total UMSARS score. [ Time Frame: 24 weeks ]
    • Change from baseline to Week 48/Termination visit in putaminal fractional anisotropy (FA) values of other brain regions on a ROI-basis [ Time Frame: 48 weeks ]
    • Change from baseline to Week 48/Termination visit in DWI abnormalities [Trace(D) and FA] of other brain regions on a ROI-basis (pons, cerebellum, middle cerebellar peduncle, caudate nucleus, globus pallidum) [ Time Frame: 48 weeks ]
    • Change from baseline in frequency and severity of putaminal atrophy, putaminal hyperintense rim, putaminal signal hypointensity, pontine atrophy, the hot cross bun sign of the pons, atrophy of the cerebellum, atrophy of the MCP and hyperintensity in MCP [ Time Frame: 48 weeks ]


    Information By: Teva Pharmaceutical Industries

    Dates:
    Date Received: September 15, 2009
    Date Started: December 2009
    Date Completion:
    Last Updated: February 10, 2015
    Last Verified: February 2015